Un mecanismo nefrogénico subyace a la poliuria inducida por dexmedetomidina: informe de un caso / Nephrogenic mechanism underlies dexmedetomidine-induced polyuria: A case report

La dexmedetomidina, agonista del adrenorreceptor α, se utiliza cada vez más como agente sedativo-hipnótico y analgésico, aunque su popularidad suscita preocupación acerca de los efectos secundarios de dicho fármaco.La bradicardia y la hipotensión son efectos adversos comunes, pero también existen diversos informes de gasto urinario excesivo, posiblemente debido a la secreción de vasopresina y a la permeabilidad de los conductos colectores.La poliuria se resuelve normalmente con la discontinuación del fármaco, no habiéndose reportado morbilidad significativa. La identificación temprana, la eliminación del agente y el tratamiento son imperativos para minimizar las complicaciones, principalmente natremia y síntomas neurológicos.Este informe de caso describe la poliuria relacionada con dexmedetomidina durante la anestesia general libre de opioides para cirugía mayor de cabeza y cuello. Nuestra hipótesis de etiología nefrogénica se ve reforzada por los datos analíticos obtenidos. También describimos cómo abordar la poliuria intraoperatoria. (AU)

Dexmedetomidine's α-adrenoreceptor agonism has been gaining popularity in the anesthetic room as a sedative-hypnotic and analgesic agent, and with extensive perioperative use rising concern about side effects is necessary.Bradycardia and hypotension are common but excessive urine output is increasingly reported, suggested mechanisms being vasopressin secretion and increasing permeability of the collecting ducts.Polyuria usually resolves with discontinuation of the drug and significant morbidity has not been reported. Early identification, removal of agent and treatment are imperative to minimize complications, mainly associated with natremia levels and neurological symptoms.This case report describes a dexmedetomidine-related polyuric syndrome during opioid-free general anesthesia for major head and neck surgery. A nephrogenic mechanism for the clinical effect is proposed and reinforced by analytical data obtained. An intra-operative polyuria approach is also delineated. (AU)

[Translated article] Postsurgical analgesic efficacy by the intra-articular administration of ropivacaine with dexmedetomidine versus simple ropivacaine in patients undergoing knee arthroscopy.

The effective relief of postsurgical pain in patients undergoing knee arthroscopy is important to allow the initiation of activities of daily living. The objective of this study is to demonstrate the analgesic efficacy of dexmedetomidine as an adjuvant added to ropivacaine by the intra-articular route. METHOD: Seventy patients underwent knee arthroscopy which were randomly assigned into two groups (n=35). The RD group received ropivacaine 1.5mg/kg plus dexmedetomidine 1µg/kg intra-articularly. Group R received ropivacaine 1.5mg/kg intra-articularly. The analgesic effect was evaluated by measuring the intensity of pain (VAS score) and the duration of analgesia. RESULTS: A longer duration of the analgesic effect was observed in the RD group (655min) compared to the R group (318min) being statistically significant (p=0.03). CONCLUSION: Dexmedetomidine as an adjuvant to intra-articular ropivacaine improves the quality and duration of postoperative analgesia in patients undergoing knee arthroscopy.

Dexmedetomidine mitigates acute kidney injury after coronary artery bypass grafting: a prospective clinical trial.

INTRODUCTION AND OBJECTIVES: To evaluate the impact of dexmedetomidine impact on cardiac surgery-associated acute kidney injury (CSA-AKI), kidney function, and metabolic and oxidative stress in patients undergoing coronary artery bypass grafting with heart-lung machine support. METHODS: A randomized double-masked trial with 238 participants (50-75 years) undergoing coronary artery bypass grafting was conducted from January 2021 to December 2022. The participants were divided into Dex (n=119) and NS (n = 119) groups. Dex was administered at 0.5 mcg/kg over 10minutes, then 0.4 mcg/kg/h until the end of surgery; the NS group received equivalent saline. Blood and urine were sampled at various time points pre- and postsurgery. The primary outcome measure was the incidence of CSA-AKI, defined as the occurrence of AKI within 96hours after surgery. RESULTS: The incidence of CSA-AKI was significantly lower in the Dex group than in the NS group (18.26% vs 32.46%; P=.014). Substantial increases were found in estimated glomerular filtration rate value at T4-T6 (P<.05) and urine volume 24hours after surgery (P<.01). Marked decreases were found in serum creatinine level, blood glucose level at T1-T2 (P<.01), blood urea nitrogen level at T3-T6 (P<.01), free fatty acid level at T2-T3 (P<.01), and lactate level at T3-T4 (P<.01). CONCLUSIONS: Dex reduces CSA-AKI, potentially by regulating metabolic disorders and reducing oxidative stress.

Sedation with propofol/remifentanil versus dexmedetomidine / remifentanil for patients undergoing transcatheter aortic valve implant: A retrospective study between 2012 and 2019.

BACKGROUND AND OBJECTIVES: Percutaneous implantation of an aortic valve prosthesis is a therapeutic alternative for patients with severe aortic stenosis. The procedure is traditionally performed under general anaesthesia; however, sedation is now gaining in popularity because it reduces the need for vasoactive drugs and shortens the patient's stay in the critical care unit and on the ward. The aim of this study is to evaluate the clinical efficacy, safety and potential benefits of sedation with dexmedetomidine in patients undergoing percutaneous implantation of an aortic valve prosthesis in terms of haemodynamic and respiratory complications. MATERIALS AND METHODS: We performed a retrospective study of 222 patients that had undergone percutaneous implantation of an aortic valve prosthesis between 2012 and 2019 under sedation with either dexmedetomidine plus remifentanil (DEX-RMF) or propofol plus remifentanil (PROPO-RMF). We collected data on complications, mainly haemodynamic and respiratory, during and after the procedure. RESULTS: No significant differences were found between sedation with dexmedetomidine and propofol (in combination with remifentanil) in terms of haemodynamic stability and intraprocedural cerebral blood oxygen. In the DEX-RMF group, however, mean blood pressure, midazolam dose, and duration of anaesthesia were lower compared with the PROPO-RMF group, but the incidence of haemodynamic and respiratory complications did not differ significantly between groups. CONCLUSIONS: Our results show that sedation, particularly with adjuvant dexmedetomidine, is a valid anaesthetic techniques in percutaneous aortic valve prosthesis implantation.

Agonistas de receptores adrenérgicos α-2, Ácido Valproico y Carbamazepina como tratamiento adyuvante en la abstinencia alcohólica moderada-grave: Revisión Sistemática / α-2 adrenergic recipients, Valproic and Carbamazepine Acids as a adjuvant treatment in moderate-grave alcoholic abstinence: Systematic Review

La dependencia del alcohol se encuentra entre los principales factores de riesgo para la salud en la mayoría de los países desarrollados y en desarrollo.El éxito terapéutico en la abstinencia modera-grave podría incrementarse con tratamiento adyuvante a las benzodiacepinas. En nuestro medio los agonistas alfa2 (clonidina y dexmedetomidina), ácido valproico y carbamazepina son los de mayor uso. El objetivo de este trabajo fue realizar la búsqueda exhaustiva, análisis crítico y resumen de la evidencia para proporcionar una visión general de la efectividad de estos fármacos cuando son utilizado sin tiempo determinado de tratamiento comparados entre sí, contra ninguna intervención, placebo u otras intervenciones. Se realizó una búsqueda bibliográfica en bases de datos (Pubmed/MEDLINE, LILACs, EMBASE). Dos revisores seleccionaron, extrajeron los datos y evaluaron el riesgo de sesgo de los estudios incluidos de forma independiente mediante el software Covidence. Los desacuerdos fueron resueltos por consenso. Realizamos metanálisis utilizando RevMan 5. 3 y análisis de subgrupos por diseño de estudio. Se incluyeron 22 estudios donde ninguno de ellos presentó bajo riesgo de sesgo en todos los dominios, y la mayoría de los estudios presentaron al menos un dominio con alto riesgo de sesgo. Estudios con resultados estadísticamente bajos mostraron que la dexmedetomidina y el ácido valproico disminuyen los requerimientos de benzodiacepinas en pacientes que recibían placebo. Además, cuando se combinan ácido valproico con benzodiacepinas logran una disminución estable y continua de la abstinencia medido en escala CIWA-Ar. La clonidina fue la única descripta que presentaba disminución en la frecuencia cardiaca frente a placebo con alta significancia, situación clínica a tener presente frente al síndrome simpaticomimético que caracteriza al síndrome de abstinencia por alcohol.

Alcohol dependence is among the main risk factors for health in most developed and developing countries. Therapeutic success in moderate-Grave abstinence could be increased with adjuvant treatment to benzodiazepines. In our environment, agonists Alfa 2 (clonidine and dexmedetomidine), valproic acid and carbamazepine are the most used. The objective of this work was to carry out the thorough search, critical analysis and summary of the evidence to provide an overview of the effectiveness of these drugs when used without a certain time of treatment compared to each other, against any intervention, placebo or other interventions. A bibliographic search was carried out in databases (Pubmed/ Medline, Lilacs, Embase). Two reviewers selected, extracted the data and evaluated the bias risk of independently included studies using the COVIDENCE software. The disagreements were resolved by consensus. We perform meta-analysis using Revman 5. 3 and subgroup analysis by study design. 22 studies were included where none of them presented under a risk of bias in all domains, and most studies presented at least one domain with high bias risk. Studies with statistically low results showed that dexmedetomidine and valproic acid decrease the requirements of benzodiazepines in patients receiving placebo. In addition, when valproic acid is combined with benzodiazepines achieve a stable and continuous decrease in abstinence measured in CIWA-AR scale. Clonidine was the only one described that presented a decrease in heart rate against placebo with high significance, clinical situation to be in mind in front of the sympathomimetic syndrome that characterizes alcohol withdrawal syndrome

A nephrogenic mechanism underlies dexmedetomidine-induced polyuria. A case report.

Dexmedetomidine's α-adrenoreceptor agonism has been gaining popularity in the anesthetic room as a sedative-hypnotic and analgesic agent, and with extensive perioperative use rising concern about side effects is necessary. Bradycardia and hypotension are common adverse effects, but there are also several reports of excessive urine output, possibly due to vasopressin secretion and permeability of collecting ducts. Polyuria usually resolves with discontinuation of the drug, and significant morbidity has not been reported. Early identification, removal of the agent, and treatment are imperative to minimize complications - mainly natremia and neurological symptoms. This case report describes a dexmedetomidine-related polyuric syndrome during opioid-free general anesthesia for major head and neck surgery. A nephrogenic mechanism for the clinical effect is proposed and reinforced by analytical data obtained. An intra-operative polyuria approach is also delineated.

Dexmedetomidina, un agonista de alfa 2, incrementa el efecto analgésico de la morfina y reduce el desarrollo de tolerancia a la morfina suprimiendo el estrés oxidativo y la vía de señalización de TNF/IL-1 en ratas / Dexmedetomidine, an alfa 2 agonist, increases the morphine analgesic effect and decreases morphine tolerance development by suppressing oxidative stress and TNF/IL-1 signalling pathway in rats

Antecedentes: El objetivo del presente estudio es examinar el posible efecto de dexmedetomidina en el desarrollo de tolerancia a la morfina en ratas, incluyendo nocicepción, analgesia con morfina, apoptosis, estrés oxidativo, y las vías del factor de necrosis tumoral (TNF)/interleucina-1 (IL-1). Materiales y métodos: En este estudio se utilizaron 36 ratas Wistar Albino (225–245 g) dividiéndose a los animales en seis grupos: solución salina (S), 20 mcg/kg de dexmedetomidina (D), 5 mg/kg de morfina (M), M + D, tolerancia a la morfina (MT), y MT + D. El efecto analgésico se midió mediante las pruebas analgésicas de placa caliente (hot-plate) y de retirada de la cola (tail-flick). Tras dichas pruebas, se extirparon los ganglios de la raíz dorsal (GRD), y se midieron en los tejidos de los mismos los parámetros del estrés oxidativo (estado antioxidante total [TAS], estado oxidante total [TOS]), TNF, IL-1 y enzimas de la apoptosis (Caspasa-3, Caspasa-9). Resultados: Dexmedetomidina reflejó un efecto antinociceptivo al administrarse en solitario (p < 0,05 a p < 0,001). Además, dexmedetomidina incrementó el efecto analgésico de la morfina (p < 0,001), y también redujo la tolerancia a la morfina a un nivel significativo (p < 0,01 a p < 0,001), reduciendo también los niveles de estrés oxidativo (p < 0,001) y TNF/IL-1 al administrarse como fármaco adicional al grupo de dosis única de morfina y tolerancia a la morfina (p < 0,001). Además, dexmedetomidina redujo los niveles de Caspasa-3 y Caspasa-9 tras el desarrollo de tolerancia (p < 0,001). Conclusión: Dexmedetomidina tiene propiedades antinociceptivas, e incrementa el efecto analgésico de la morfina, previniendo también el desarrollo de tolerancia. Estos efectos se producen probablemente debido a la modulación del estrés oxidativo, la inflamación y la apoptosis.(AU)

Background: The aim of the present study is to examine the possible effect de dexmedetomidine on the development of morphine tolerance in rats including nociception, morphine analgesia, apoptosis, oxidative stress, and tumour necrosis factor (TNF)/ interleukin-1 (IL-1) pathways. Materials and methods: In this study, 36 Wistar Albino (225–245 g) rats were used. Animals were divided into 6 groups: saline (S), 20 mcg/kg dexmedetomidine (D), 5 mg/kg morphine (M), M + D, morphine tolerance (MT), and MT + D. The analgesic effect was measured with hot plate and tail-flick analgesia tests. After the analgesia tests, the dorsal root ganglia (DRG) tissues were excised. Oxidative stress parameters [total antioxidant status (TAS), total oxidant status (TOS)], TNF, IL-1 and apoptosis enzymes (Caspase-3, Caspase-9), were measured in DRG tissues. Results: Dexmedetomidine showed an antinociceptive effect when given alone (p < 0.05 to p < 0.001). In addition, dexmedetomidine increased the analgesic effect of morphine (p < 0.001), and also decreased the tolerance to morphine at a significant level (p < 0.01 to p < 0.001). Moreover, it decreased oxidative stress (p < 0.001) and TNF/IL-1 levels when given as an additional drug of single-dose morphine and morphine tolerance group (p < 0.001). Furthermore, dexmedetomidine decreased Caspase-3 and Caspase-9 levels after tolerance development (p < 0.001). Conclusión: Dexmedetomidine has antinociceptive properties, and it increases the analgesic effect of morphine and also prevents tolerance development. These effects probably occur by the modulation of oxidative stress, inflammation and apoptosis.(AU)

Dexmedetomidine, an α2 agonist, increases the morphine analgesic effect and decreases morphine tolerance development by suppressing oxidative stress and TNF/IL-1 signalling pathway in rats.

BACKGROUND: The aim of the present study is to examine the possible effect de dexmedetomidine on the development of morphine tolerance in rats including nociception, morphine analgesia, apoptosis, oxidative stress, and tumour necrosis factor (TNF)/ interleukin-1 (IL-1) pathways. MATERIALS AND METHODS: In this study, 36 Wistar Albino (225-245 g) rats were used. Animals were divided into 6 groups: saline (S), 20 mcg/kg dexmedetomidine (D), 5 mg/kg morphine (M), M + D, morphine tolerance (MT), and MT + D. The analgesic effect was measured with hot plate and tail-flick analgesia tests. After the analgesia tests, the dorsal root ganglia (DRG) tissues were excised. Oxidative stress parameters [total antioxidant status (TAS), total oxidant status (TOS)], TNF, IL-1 and apoptosis enzymes (Caspase-3, Caspase-9), were measured in DRG tissues. RESULTS: Dexmedetomidine showed an antinociceptive effect when given alone (p < 0.05 to p < 0.001). In addition, dexmedetomidine increased the analgesic effect of morphine (p < 0.001), and also decreased the tolerance to morphine at a significant level (p < 0.01 to p < 0.001). Moreover, it decreased oxidative stress (p < 0.001) and TNF/IL-1 levels when given as an additional drug of single-dose morphine and morphine tolerance group (p < 0.001). Furthermore, dexmedetomidine decreased Caspase-3 and Caspase-9 levels after tolerance development (p < 0.001). CONCLUSION: Dexmedetomidine has antinociceptive properties, and it increases the analgesic effect of morphine and also prevents tolerance development. These effects probably occur by the modulation of oxidative stress, inflammation and apoptosis.

Mastectomía libre de opioides bajo anestesia-analgesia epidural torácica en un paciente con estenosis traqueal crítica: caso clínico / Opioid-free mastectomy under thoracic epidural anesthesia-analgesia in a patient with critical tracheal stenosis: A case report

Mastectomy is traditionally performed under general anaesthesia and invasive ventilation, and is often complemented with regional techniques. In this setting, tracheal stenosis can pose a challenge to airway management. The aim of this report is to describe the successful management of a 68-year-old woman with severe subglottic tracheal stenosis undergoing mastectomy due to breast cancer. Surgery was performed without airway instrumentation under an opioid-free regimen consisting of thoracic epidural, propofol and dexmedetomidine perfusion, and non-opioid analgesics. Spontaneous ventilation and adequate perioperative analgesia were achieved. Opioid-free anaesthesia without airway instrumentation, consisting of thoracic epidural anaesthesia and sedation, is a good alternative in patients undergoing mastectomy in whom airway manipulation is best avoided.(AU)

La mastectomía se realiza tradicionalmente bajo anestesia general y ventilación invasiva, complementándose a menudo con técnicas regionales. En este contexto, la estenosis traqueal puede suponer un reto para el manejo de la vía aérea. El objetivo de este informe es describir el manejo exitoso de una mujer de 68 años de edad con estenosis traqueal subglótica severa, sometida a mastectomía debido a cáncer de mama. La cirugía se realizó sin instrumentación de la vía aérea bajo un régimen libre de opioides consistente en epidural torácica, propofol y perfusión de dexmedetomidina, y analgésicos no opioides, lográndose ventilación espontánea y analgesia perioperatoria adecuada. La anestesia libre de opioides sin instrumentación de la vía aérea, consistente en anestesia epidural torácica y sedación, es una buena alternativa en pacientes sometidos a mastectomía, en los que es mejor evitar la manipulación de la vía aérea.(AU)

Opioid-free mastectomy under thoracic epidural anesthesia-analgesia in a patient with critical tracheal stenosis: a case report.

Mastectomy is traditionally performed under general anaesthesia and invasive ventilation, and is often complemented with regional techniques. In this setting, tracheal stenosis can pose a challenge to airway management. The aim of this report is to describe the successful management of a 68-year-old woman with severe subglottic tracheal stenosis undergoing mastectomy due to breast cancer. Surgery was performed without airway instrumentation under an opioid-free regimen consisting of thoracic epidural, propofol and dexmedetomidine perfusion, and non-opioid analgesics. Spontaneous ventilation and adequate perioperative analgesia were achieved. Opioid-free anaesthesia without airway instrumentation, consisting of thoracic epidural anaesthesia and sedation, is a good alternative in patients undergoing mastectomy in whom airway manipulation is best avoided.

The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain / O efeito da dexmedetomidina na expressão do óxido nítrico sintase neuronal na medula espinhal dorsal em um modelo rato com dor neuropática crônica

Abstract Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4-6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

Resumo Antecedentes A dor neuropática refere-se tipicamente à dor causada por lesões ou doenças do sistema somatossensorial. De modo geral, é caracterizada por dor à ambulação, alodinia e hiperalgesia. O óxido nítrico produzido pela enzima óxido nítrico sintase neuronal (nNOS) na medula espinhal dorsal pode ter um papel predominante na regulação da dor neuropática. A alta eficácia e segurança, bem como a plausível capacidade de proporcionar conforto, faz com que a dexmedetomidina (DEX) seja um adjuvante anestésico eficaz. O objetivo deste estudo foi investigar o efeito da DEX na expressão de nNOS na medula espinhal dorsal em um modelo de ratos com dor neuropática crônica. Métodos Ratos Sprague Dawley (SD) machos foram distribuídos aleatoriamente em três grupos: grupo de cirurgia simulada (sham), grupo de cirurgia (do nervo ciático; CCI) e grupo dexmedetomidina (DEX). Os modelos de dor neuropática crônica nos grupos CCI e DEX foram estabelecidos por ligadura do nervo ciático. A latência de retirada térmica (TWL) foi medida no dia 1 antes da cirurgia e nos dias 1, 3, 7 e 14 após o procedimento. Seis animais de cada grupo foram eutanasiados após a medida de TWL nos dias 7 e 14 após a cirurgia e o segmento L4-6 da medula espinhal foi extraído para determinação da expressão de nNOS por imuno-histoquímica. Resultados Em comparação ao grupo sham, o limiar de TWL diminuiu significativamente e a expressão de nNOS foi regulada de maneira positiva após a cirurgia nos grupos CCI e DEX. Comparado ao grupo CCI, o limiar de TWL aumentou de forma significativa e a expressão de nNOS caiu significativamente diminuída nos dia 7 e 14 após a cirurgia no grupo DEX. Conclusão A regulação negativa de nNOS na medula espinhal dorsal está envolvida na atenuação da dor neuropática pela DEX.

Dexmedetomidina vía nasal en colecistectomía laparoscópica / Dexmedetomidine intranasally in laparoscopic cholecystectomy

Resumen: Introducción: la dexmedetomidina es un adyuvante en el manejo anestésico perioperatorio y si se administra por vía nasal las dosis requeridas tienen mínimos efectos secundarios. Material y métodos: ensayo clínico aleatorizado doble ciego en pacientes sometidos a colecistectomía laparoscópica con anestesia general, comparando la dexmedetomidina intranasal (1 μg/kg de peso ideal) contra placebo, se comparó el efecto analgésico postoperatorio por medio de la escala visual análoga del dolor (EVA) y el consumo de opioides transanestésico. El análisis estadístico se realizó con t de Student y exacta de Fisher. Resultados: se incluyeron 54 pacientes aleatorizados en dos grupos: dexmedetomidina y control. El 81.5% de los sujetos fueron mujeres, no se encontró diferencia entre los grupos en las variables demográficas. La media de la calificación EVA a los 60 minutos para el grupo dexmedetomidina fue (2.89 ± 1.9), estadísticamente inferior comparada contra el grupo control (5.78 ± 2.3) (p ˂ 0.0001). El consumo de opioides para dexmedetomidina fue (0.424 ± 0.074 μg/h) estadísticamente menor al control (0.697 ± 0.136 μg/h) (p ˂ 0.0001) con un tamaño del efecto de Cohen de 250%. Conclusiones: disminución significativa en EVA y en el consumo de opioides con el uso de dexmedetomidina intranasal en colecistectomía laparoscópica.

Abstract: Introduction: dexmedetomidine is and useful adjuvant agent in the perioperative anesthetic management associated to nasal administration with minimum adverse effects. Material and methods: a randomized, controlled, double blind, clinical trial was carried out in elective patients undergoing laparoscopic cholecystectomy with general anesthesia. Aim of this study was to compare the postoperative analgesic effect through visual analogue scale (VAS) and the perioperative opioid consumption. Dexmedetomidine was administrated intranasally (1 μg/kg dose) versus placebo. Statistical analysis was realized through student t and Fisher Test. Results: 54 patients were randomized in two groups: dexmedetomidine vs control. Not significant differences were found between both groups in demographic variables but 81.5% were women. Mean of VAS score at 60 minutes was significantly inferior (2.89 ± 1.9) versus control group (5.78 ± 2.3) (p ˂ 0.0001). Mean of opioids consumption in dexmedetomidine group (0.424 ± 0.074 μg/h) was significant minor of control group (0.697 ± 0.136 μg/h) (p ˂ 0.0001). Size effect through Cohen test was 250%. Conclusion: statistically decrease in VAS and in opioid consumption was observed using dexmedetomidine nasally in laparoscopic cholecystectomy.

O Pré-Condicionamento com Dexmedetomidina Atenua a Lesão de Isquemia/Reperfusão Miocárdica em Ratos, Suprimindo a Mitofagia Via Ativação do Receptor Α2-Adrenérgico / Dexmedetomidine Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury in Rats by Suppressing Mitophagy Via Activating Α2-Adrenergic Receptor

Resumo Fundamento A dexmedetomidina (DEX), um agonista específico do receptor α2-adrenérgico, é protetora contra lesão de isquemia/reperfusão miocárdica (I/R). No entanto, a associação entre a cardioproteção induzida pelo pré-condicionamento DEX e a supressão da mitofagia permanece pouco clara. Objetivo Portanto, nosso objetivo foi investigar se o pré-condicionamento com DEX alivia a I/R, suprimindo a mitofagia via ativação do receptor α2-adrenérgico. Método Sessenta corações de ratos isolados foram tratados com ou sem DEX antes de induzir isquemia e reperfusão; um antagonista do receptor α2-adrenérgico, a ioimbina (YOH), também foi administrado antes da isquemia, isoladamente ou com DEX. A frequência cardíaca (FC), pressão diastólica do ventrículo esquerdo (PDVE), pressão diastólica final do ventrículo esquerdo (PDFVE), taxa máxima e mínima de desenvolvimento da pressão ventricular esquerda (±dp/dtmax) e tamanho do infarto do miocárdio foram medidos. A ultraestrutura mitocondrial e as autofagossomas foram avaliadas por microscopia eletrônica de transmissão. O potencial de membrana mitocondrial e os níveis de espécies reativas de oxigênio (ROS) foram medidos usando os ensaios JC-1 e diacetato de diclorodi hidrofluoresceína, respectivamente. Os níveis de expressão das proteínas associadas à mitofagia Beclin1, relação LC3II/I, p62, PINK1 e Parkin foram detectados por western blotting. Resultados Em comparação com o grupo controle, no grupo isquemia/reperfusão, a FC, PDVE e ±dp/dtmax foram notavelmente diminuídas (p<0,05), enquanto os tamanhos da PDFVE e do infarto aumentaram significativamente (p<0,05). O pré-condicionamento com DEX melhorou significativamente a disfunção cardíaca, reduziu o tamanho do infarto do miocárdio, manteve a integridade estrutural mitocondrial, aumentou o potencial de membrana mitocondrial, inibiu a formação de autofagossomas e diminuiu a produção de ROS e a relação Beclin1, relação LC3II/I, expressão PINK1, Parkin e p62(p<0,05). Quando DEX e YOH foram combinados, o YOH cancelou o efeito da DEX, enquanto o uso de YOH sozinha não teve efeito. Conclusão Portanto, o pré-condicionamento DEX foi cardioprotetor contra I/R em ratos, suprimindo a mitofagia por meio da ativação do receptor α2-adrenérgico.

Abstract Background Dexmedetomidine (DEX), a specific α2-adrenergic receptor agonist, is protective against myocardial ischemia/reperfusion injury (MIRI). However, the association between DEX preconditioning-induced cardioprotection and mitophagy suppression remains unclear. Objective Hence, we aimed to investigate whether DEX preconditioning alleviates MIRI by suppressing mitophagy via α2-adrenergic receptor activation. Method Sixty isolated rat hearts were treated with or without DEX before inducing ischemia and reperfusion; an α2-adrenergic receptor antagonist, yohimbine (YOH), was also administered before ischemia, alone or with DEX. The heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal and minimal rate of left ventricular pressure development (±dp/dtmax), and myocardial infarction size were measured. The mitochondrial ultrastructure and autophagosomes were assessed using transmission electron microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using JC-1 and dichloride hydrofluorescein diacetate assays, respectively. The expression levels of the mitophagy-associated proteins Beclin1, LC3II/I ratio, p62, PINK1, and Parkin were detected by western blotting. Results Compared with the control group, in the ischemia/reperfusion group, the HR, LVDP, and ±dp/dtmax were remarkably decreased (p< 0.05), whereas LVEDP and infarct sizes were significantly increased (p< 0.05). DEX preconditioning significantly improved cardiac dysfunction reduced myocardial infarction size, maintained mitochondrial structural integrity, increased mitochondrial membrane potential, inhibited autophagosomes formation, and decreased ROS production and Beclin1, LC3II/I ratio, PINK1, Parkin, and p62 expression(p< 0.05). When DEX and YOH were combined, YOH canceled the effect of DEX, whereas the use of YOH alone had no effect. Conclusion Therefore, DEX preconditioning was cardioprotective against MIRI in rats by suppressing mitophagy via α2-adrenergic receptor activation.

Postsurgical analgesic efficacy by the intra-articular administration of ropivacaine with dexmedetomidine versus simple ropivacaine in patients undergoing knee arthroscopy. / Eficacia analgésica posquirúrgica en la administración intraarticular de ropivacaína con dexmedetomidina en comparación con ropivacaína simple en pacientes intervenidos de artroscopia de rodilla.

The effective relief of postsurgical pain in patients undergoing knee arthroscopy is important to allow the initiation of activities of daily living. The objective of this study is to demonstrate the analgesic efficacy of dexmedetomidine as an adjuvant added to ropivacaine by the intra-articular route. METHOD: Seventy patients underwent knee arthroscopy which were randomly assigned into two groups (n=35). The RD group received ropivacaine 1.5mg/kg plus dexmedetomidine 1µg/kg intra-articularly. Group R received ropivacaine 1.5mg/kg intra-articularly. The analgesic effect was evaluated by measuring the intensity of pain (VAS score) and the duration of analgesia. RESULTS: A longer duration of the analgesic effect was observed in the RD group (655min) compared to the R group (318min) being statistically significant (p=0.03). CONCLUSION: Dexmedetomidine as an adjuvant to intra-articular ropivacaine improves the quality and duration of postoperative analgesia in patients undergoing knee arthroscopy.

A randomized comparison between interscalene block and dexmedetomidine for arthroscopic shoulder surgery / Una comparación aleatoria entre el bloqueo interescalénico y dexmedetomidina para la cirugía artroscópica de hombro

Abstract Introduction: Management of intraoperative hemodynamics and postoperative analgesia during arthroscopic shoulder surgeries remains a challenge. Although interscalene brachial plexus block (ISB) is considered ideal for shoulder anesthesia it requires skill and proficiency unlike intravenous (IV) dexmedetomidine. Objective: This randomized trial was performed to observe the efficacy of dexmedetomidine infusion which is less invasive and demands lesser skills than plexus block. Methodology: All patients scheduled for elective arthroscopic shoulder surgery under general anesthesia were assigned either to group DEX, which received an IV dexmedetomidine bolus of 0.5 mcg/kg over 20 minutes, followed by an infusion of 0.5 mcg/kg/hour that was stopped 30 minutes before surgery the end of surgery or to group BLOCK which received ultrasound guided ISB with 20ml of 0.25% bupivacaine. The primary outcome assessed was intraoperative hemodynamics; the secondary outcomes were immediate postoperative pain, operating condition as assessed by the surgeon, recovery time, and patient satisfaction after 24 hours. Blinded investigator and composite scores were used for the assessment. Results: Both groups displayed equivalent scores for intraoperative hemodynamics whereas ISB resulted in a better post-operative analgesia (p < 0.001). Surgeon's opinion and recovery time were comparable. Overall, the patients had a satisfactory experience with both techniques, according to the quality assessment. Conclusions: IV dexmedetomidine infusion is an effective alternative to ISB for reconstructive shoulder surgeries under general anesthesia.

Resumen Introducción: El manejo hemodinámico intraoperatorio y la analgesia postoperatoria durante la cirugía artroscópica de hombro sigue siendo un desafío. Aun cuando el bloqueo interescalénico del plexo braquial (BIE) se considera ideal para la anestesia del hombro, a diferencia del uso de la dexmedetomidina intravenosa (IV), el BIE requiere destreza y maestría. Objetivo: El presente estudio aleatorizado se llevó a cabo para observar la eficacia de la infusión de dexmedetomidina que es menos invasiva y exige menos destreza que el bloqueo del plexo. Metodología: Todos los pacientes programados para cirugía artroscópica electiva de hombro bajo anestesia general, se asignaron o bien al grupo DEX, para recibir un bolo de dexmedetomidina IV de 0,5 mcg/kg en 20 minutos, seguido de una infusión de 0,5 mcg/kg/hora que se detuvo 30 minutos antes del final de la cirugía; o, al grupo BLOQUEO al cual se le administró un BIE ecoguiado con 20ml debupivacaína 0,25%. El desenlace primario evaluado fue la hemodinamia intraoperatoria; los desenlaces secundarios fueron el dolor postoperatorio inmediato, la condición operatoria evaluada por el cirujano, el tiempo de recuperación y la satisfacción del paciente después de 24 horas. Para la evaluación se utilizaron el investigador ciego y puntajes compuestos. Resultados: Ambos grupos mostraron puntajes equivalentes en la hemodinamia intraoperatoria, en tanto que el BIE dio como resultado una mejor analgesia en el postoperatorio (p < 0.001). La opinión del cirujano y el tiempo de recuperación fueron comparables. En general, la experiencia de los pacientes fue satisfactoria con ambas técnicas, de acuerdo con la evaluación de calidad. Conclusiones: La infusión de dexmedetomidina IV es una alternativa efectiva al BIE para cirugías reconstructivas de hombro bajo anestesia general.

Dexmedetomidina y analgesia perioperatoria en niños / Dexmedetomidine and perioperative analgesia in children

La dexmedetomidina (DEX) es un agente anestésico que mimetiza el sueño profundo natural y produce una mínima depresión cardiorrespiratoria, convirtiéndose en una opción muy valiosa en el manejo de un paciente tan exigente como es el pediátrico. El objetivo principal de esta mini revisión fue centrarse en el papel de la DEX como analgésico en el período perioperatorio de niños sometidos a anestesia. Se realizó una búsqueda bibliográfica, entre 2010 y 2021, en Google, Pubmed, Embase y Cochrane Library. Se repasaron diferentes aspectos como su farmacología, efectividad, seguridad y la evidencia más reciente sobre su uso clínico como analgésico en anestesia pediátrica. Igualmente se incluyó una estimación de coste del tratamiento analgésico perioperatorio con DEX.(AU)

Dexmedetomidine (DEX) is an anaesthetic agent that mimics natural deep sleep and produces minimal cardiorespiratory depression. As such, it is a very valuable option in the management of such a challenging population as paediatric patients. The main objective of this mini review was to evaluate the role of DEX as a perioperative analgesic in children receiving anaesthesia. We searched Google, Pubmed, Embase and the Cochrane Library for articles published between 2010 and 2021, and reviewed various of aspects of DEX, such as pharmacology, effectiveness, safety, and the most recent evidence on its clinical use as an analgesic in paediatric anaesthesia. We also include a cost estimate of perioperative analgesia with DEX.(AU)

Dexmedetomidine and perioperative analgesia in children.

Dexmedetomidine (DEX) is an anaesthetic agent that mimics natural deep sleep and produces minimal cardiorespiratory depression. As such, it is a very valuable option in the management of such a challenging population as paediatric patients. The main objective of this mini review was to evaluate the role of DEX as a perioperative analgesic in children receiving anaesthesia. We searched Google, Pubmed, Embase and the Cochrane Library for articles published between 2010 and 2021, and reviewed various of aspects of DEX, such as pharmacology, effectiveness, safety, and the most recent evidence on its clinical use as an analgesic in paediatric anaesthesia. We also include a cost estimate of perioperative analgesia with DEX.

Awake pronation with helmet continuous positive airway pressure for COVID-19 acute respiratory distress syndrome patients outside the ICU: A case series.

OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.

Anaesthetic management in neurosurgery in a patient with Eisenmenger syndrome and Down syndrome. A case report.

Adults patients with congenital heart disease increasingly present for non cardiac surgery. The anesthetic management this type of patients in neurosurgery requires a meticulous surgical anesthetic planning. The need for urgent intervention, with the presence of a congenital heart disease evolved to Eisenmenger syndrome, associated to a difficult airway, is a challenge for the anesthesiologist. The use of dexmedetomidine may be a valid alternative. We present the case of a patient with Down syndrome, and Eisenmenger syndrome who underwent drainage of brain abscess from the emergency department and was subsequently scheduled for reintervention. We compare the different anesthetic techniques used in both procedures, analyzing the implications they had on the main physiopathological alterations presented by the patient.